In chemical reaction processes, methods of separating as a solid a specified component dissolved in a liquid are widely used. This is because, by solidifying (crystallizing) only the specified component, separation and/or purification after the reaction are simplified. In particular, recently, in successive multistage synthesis such as compound library synthesis and the like used in the research and development of pharmaceuticals, after the completion of each reaction, by solidifying (crystallizing) the unnecessary compounds, the removal of the solidified (crystallized) substances becomes easy, and it is possible to prevent the processes from becoming complicated.
The solidification (crystallization) of specified components dissolved in a solution in this way is implemented by satisfying defined conditions in the relationship with chemical properties and physical properties of the compounds, and with the solvent.
However, the conditions for solidification (crystallization), in many cases, must be found by experience based on trial and error. Especially, in successive multistage synthesis, because it is necessary to consider the solidification (crystallization) conditions based on the characteristic properties of the compounds synthesized in each of the stages, process development is very expensive and time consuming.
In order to solve such problems, in the prior art, there was known a means of using a chemically modified reagent on polystyrene or silica, and separating the liquid including the products, and the reagents, by filtration after the reaction. With these reagents, it is possible to easily separate unreacted compounds added in excess, byproducts, and catalysts, in an organic synthesis reaction or the like, without complicated separation processes.
Further, Patent Document 1 discloses a method for practicing a nucleophilic substitution reaction (Mitsunobu reaction) of an alcohol for producing a desired product, including a step of reacting an alcohol and a nucleophilic reagent with an azodicarboxylate and a phosphine, wherein at least one of the azodicarboxylate and phosphine include at least one fluorous tag (a retention group of a highly fluorinated alkyl group or the like). Here, for example, fluorous solvents including perfluorocarbon or the like, will be present as a third phase without mixing with organic solvents or water, and have the characteristic of dissolving compounds having a fluorous tag. Because of this, by adding a fluorous solvent to a uniform reaction phase, it is possible to easily separate a compound which must be separated from the product, and which has a fluorous tag.
Further, by using a fluorous carrier which selectively bonds to a fluorous tag, it is possible to easily separate a compound having a fluorous tag by solid-liquid extraction.
Patent Document 1: Japanese Publication No. 2005-508890 of PCT Application.